[The acute and chronic effects of 50 mg of isosorbide 5-mononitrate with delayed action in patients with stable angina of effort]. / Estudio del efecto agudo y crónico de 50 mg de 5-mononitrato de isosorbida de liberación retardada en pacientes con angina de esfuerzo estable.

ABSTRACT

In 10 patients with stable effort angina and angiographically demonstrated coronary artery disease, serial exercise test were performed in order to assess the efficacy and duration of the anti-ischemic effects of a single dose (50 mg) of a sustained-release preparation of 5-isosorbide mononitrate (5-IMN). The possible presence of a tolerance phenomenon was also sought. The study was randomized, double-blind and placebo-controlled. Four hours after an acute dose of 5-IMN, time for -1 mm ST segment depression significatively increased as compared with basal test and placebo test (367 +/- 92 vs 199 +/- 87 and 250 +/- 78 sec respectively, p less than 0.0004). At the same test, total exercise time also increased from 282 +/- 92 sec (basal) and 323 +/- 91 sec (placebo) to 424 +/- 91 sec (p less than 0.008). At 12 hours test, total exercise time was also significantly increased as compared with basal test and placebo test (354 +/- 109 vs 282 +/- 92 and 291 +/- 90 sec respectively; p less than 0.01). These effects were not present when the patients were tested 24 hours after active drug administration. After daily administration of a single dose of 5-IMN during a 3 week period, 4 and 12 hours test demonstrated a persistent and significant anti-ischemic effect, similar to the acute figures. Thus, an acute dose of 50 mg of a sustained-release preparation of 5-IMN reveals significant anti-ischemic effects which remain 4 and 12 hours after drug administration. Chronic administration of the preparation for 3 weeks (single daily dose) is equally effective, without any evidence of tolerance phenomenon.